Mutation induction in repair-deficient strains of Drosophila.
Experimental evidence indicates a polygenic control of mutagenesis in Drosophila melanogaster. In oocytes chromosome aberrations detected as half-translocations or dominant lethals depend on a repair system which in a number of genetically nonrelated strains shows different repair capacities. Sister chromatic exchanges (SCE) are easily studied as ring chromosome losses. They develop through a genotype controlled mechanism from, premutational lesions. Stocks with particular pairs of third chromosomes were discovered in which increased sensitivity of larvae to the toxic effects of a monofunctional alkylating agent (MMS) correlates with high frequencies of x-ray induced SCE's. Sex-linked mutagen-sensitive mutants could be shown to control mutation fixation: Pronounced maternal effects were found when sperm carrying particular types of premutational lesions were introduced into different types of mutant oocytes. The mutant mus(1)101D1 was found to be unable to process lesions induced by the crosslinking agent nitrogen mustard (HN2) into point mutations (measured as sex-linked recessive lethals). Alkylation damage leads to increased point mutation frequencies in the excision repair deficient mutant mei-9L1, but to reduced frequencies in the post-replication repair deficient mutant mei-41D5. It became clear that the study of maternal effects on mutagenized sperm represents an efficient tool to analyze the genetic control of mutagenesis in the eukaryotic genome of Drosophila melanogaster.
D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D002869:Chromosome Aberrations; D004260:DNA Repair; D004331:Drosophila melanogaster / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D005260:Female; D005799:Genes, Dominant; D007814:Larva / Q000187:drug effects; D008297:Male; D008466:Mechlorethamine / Q000494:pharmacology; D009154:Mutation; D009865:Oocytes / Q000378:metabolism; D012737:Sex Factors; D012854:Sister Chromatid Exchange; D013094:Spermatozoa / Q000187:drug effects / Q000528:radiation effects
D000477:Alkylating Agents; D008466:Mechlorethamine